Gene regulation by melatonin linked to epigenetic phenomena

Korkmaz, Ahmet; Rosales-Corral, Sergio; Reíter, Russel J.

doi:10.1016/j.gene.2012.04.040

Cited by 109 publications

(108 citation statements)

References 173 publications

(190 reference statements)

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“…The action of melatonin on gene expression seems complex and sometimes opposite effects are observed (Fustin et al, 2009;Korkmaz et al, 2012). Thus, melatonin can induce or suppress gene expression under the same conditions (Mayo et al, 2002;Fustin et al, 2009;Korkmaz et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Melatonin and Its Analog 5-Methoxycarbonylamino-N-Acetyltryptamine Potentiate Adrenergic Receptor-Mediated Ocular Hypotensive Effects in Rabbits: Significance for Combination Therapy in Glaucoma

Crooke

Huete-Toral

Martínez-Águila

et al. 2013

J Pharmacol Exp Ther

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Melatonin is currently considered a promising drug for glaucoma treatment because of its ocular hypotensive and neuroprotective effects. We have investigated the effect of melatonin and its analog 5-methoxycarbonylamino-N-acetyltryptamine, 5-MCA-NAT, on b 2 /a 2A -adrenergic receptor mRNA as well as protein expression in cultured rabbit nonpigmented ciliary epithelial cells. Quantitative polymerase chain reaction and immunocytochemical assays revealed a significant b 2 -adrenergic receptor downregulation as well as a 2A -adrenergic receptor up-regulation of treated cells (P , 0.001, maximal significant effect). In addition, we have studied the effect of these drugs upon the ocular hypotensive action of a nonselective b-adrenergic receptor (timolol) and a selective a 2 -adrenergic receptor agonist (brimonidine) in normotensive rabbits. Intraocular pressure (IOP) experiments showed that the administration of timolol in rabbits pretreated with melatonin or 5-MCA-NAT evoked an additional IOP reduction of 14.02% 6 5.8% or 16.75% 6 5.48% (P , 0.01) in comparison with rabbits treated with timolol alone for 24 hours. Concerning brimonidine hypotensive action, an additional IOP reduction of 29.26% 6 5.21% or 39.07% 6 5.81% (P , 0.001) was observed in rabbits pretreated with melatonin or 5-MCA-NAT when compared with animals treated with brimonidine alone for 24 hours. Additionally, a sustained potentiating effect of a single dose of 5-MCA-NAT was seen in rabbits treated with brimonidine once daily for up 4 days (extra IOP decrease of 15.57% 6 5.15%, P , 0.05, compared with brimonidine alone). These data confirm the indirect action of melatoninergic compounds on adrenergic receptors and their remarkable effect upon the ocular hypotensive action mainly of a 2 -adrenergic receptor agonists but also of b-adrenergic antagonists.

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Section: Discussionmentioning

confidence: 99%

Melatonin and Its Analog 5-Methoxycarbonylamino-N-Acetyltryptamine Potentiate Adrenergic Receptor-Mediated Ocular Hypotensive Effects in Rabbits: Significance for Combination Therapy in Glaucoma

Crooke

Huete-Toral

Martínez-Águila

et al. 2013

J Pharmacol Exp Ther

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“…CREB-binding protein (CBP) and P300 are transcriptional activators that have HAT properties (58). The CBP/P300 complex recruits a number of transcriptional co-activators, such as NF-kB, CREB, and nuclear factor erythroid 2-related factor 2 (Nrf-2), for transcription (59). Melatonin suppresses P300 HAT activity (60) and thereby NF-kB acetylation and binding to the promoters of some inflammatory genes (61).…”

Section: Melatonin During Agingmentioning

confidence: 99%

“…Melatonin suppresses P300 HAT activity (60) and thereby NF-kB acetylation and binding to the promoters of some inflammatory genes (61). The expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) is regulated by NF-kB and inhibited by melatonin (59). In addition to NF-kB suppression, the enzyme COX-2, which converts arachidonic acid to prostaglandin H2 in inflammation and tumorigenesis, is suppressed by melatonin (61).…”

Section: Melatonin During Agingmentioning

confidence: 99%

“…COX-2 is distributed in specific areas of the brain, including the hippocampus, and is involved in learning and memory (62). Thus, by suppressing CBP/P300 HAT activity, melatonin promotes the anti-inflammatory effect via epigenetic mechanisms and also stimulates the expression of the transcription factor Nrf2, which promotes the expression of some antioxidant genes (59). The anti-inflammatory and antioxidant roles of melatonin can also be explained by the upregulation of Nrf-2, which is involved in both pathways (63) via CBP/P300-mediated acetylation (64).…”

Section: Melatonin During Agingmentioning

confidence: 99%

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Effects of Melatonin on Nervous System Aging: Neurogenesis and Neurodegeneration

et al. 2013

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Abstract. Neural aging as a progressive loss of function involves central and peripheral postmitotic neurons and neural stem cells (NSCs). It promotes neurodegeneration, impairs neurogenesis, and can be considered a cause of cognitive impairment and sensory and motor deficits in the elderly. Age-related morphological atrophic changes and cellular alterations are addressed by neural aging mechanisms. Neurogenesis declines during aging through several mechanisms such as an increase in quiescence state, changes in lineage fate, telomerase dysfunction, the failure of the DNA repair system, increased apoptosis, and the impairment of self-renewal. The selfrenewal transcriptional factor Sox2 has been correlated with retrotransposon L1 and certain cellcycle-and epigenetic-related factors, which are sometimes considered age-related factors in NSC aging. As neurogenesis decreases, non-mitotic neurons undergo neurodegeneration by oxidative stress, sirtuin, insulin signaling and mTOR alteration, mitochondrial dysfunction, and protein misfolding and aggregation. As neurodegeneration and impaired neurogenesis promote the nervous system aging process, the identification of neuronal anti-aging is required to raise life expectancy. The role of melatonin in increasing neurogenesis and protecting against neurodegeneration has been investigated. Here, we review nervous system aging that is correlated with mechanisms of neurodegeneration and the impairment of neurogenesis and evaluate the effects of melatonin on these processes.

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“…In melatonin research, this is an emerging field [1][2][3]. Among the multiple epigenetic changes, the contribution of microRNAs (miRNAs) as regulators of countless functions is of particular interest [4][5][6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Interactions of Melatonin and MicroRNAs

Hardel¹

2018

Biochem Mol biol J

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MicroRNAs (miRNAs) are important players in the modulation of cellular functions and contribute substantially to epigenetic changes in the expression of genes. Moreover, the distribution of miRNAs via exosomes and ectosomes opens a vast field of intraorganismal communication, with the potential of spreading pathological deviations, but also curative effects induced by protective agents. Interactions between melatonin and microRNAs are of particular interest, as melatonin is a highly pleiotropic regulator of numerous functions in every organ. The effects of melatonin in correcting pathological alterations in miRNA composition are reviewed, along with the corresponding reversal of cell biological or physiological functions to normal. Additionally, knowledge on the influence of miRNAs on melatonin formation and expression of a melatonin receptor has been considered. The fields in which melatonin has been shown to influence miRNAs are as diverse as metabolic syndrome, liver steatosis, immunology, amyloid toxicity, progenitor cells, and cancer. Readers are encouraged to contribute to systematic studies on melatonin effects on miRNAs using modern RNA sequencing techniques.

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Gene regulation by melatonin linked to epigenetic phenomena

Cited by 109 publications

References 173 publications

Melatonin and Its Analog 5-Methoxycarbonylamino-N-Acetyltryptamine Potentiate Adrenergic Receptor-Mediated Ocular Hypotensive Effects in Rabbits: Significance for Combination Therapy in Glaucoma

Melatonin and Its Analog 5-Methoxycarbonylamino-N-Acetyltryptamine Potentiate Adrenergic Receptor-Mediated Ocular Hypotensive Effects in Rabbits: Significance for Combination Therapy in Glaucoma

Effects of Melatonin on Nervous System Aging: Neurogenesis and Neurodegeneration

Interactions of Melatonin and MicroRNAs

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